Mild Cognitive ImpairmentPhase 2NCT02813070
Comparison of PET Amyloid Imaging in Japanese and Western Subjects
A Phase 2 study testing [18F] Flutemetamol in people with Mild Cognitive Impairment and Alzheimer's Disease, run by GE Healthcare.
Trial summary
This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: healthy volunteers (HV), amnestic mild cognitive impairment (aMCI), and probable Alzheimer's disease (pAD), and to assess the reproducibility of brain uptake and of image… Read more about this study
- Who is it for?
- Ages 25 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment, Alzheimer's Disease, Healthy
- What is being tested?
- [18F] Flutemetamol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- No sites listed yet
- Study dates
- Oct 2012to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General inclusion criteria for all subjects:
- The subject had at least 6 years of education.
- The subject was of first-order Japanese descent.
- The subject exhibited adequate visual, auditory and communication capabilities, and was willing and able to complete standard tests of cognitive function.
- The subject's general health was adequate to comply with all study procedures, as ascertained by review of their medical history, and laboratory and physical examinations, which was performed within 45 days before the first administration of Flutemetamol F 18 Injection.
- The subject (and the caregiver, if relevant) was/were compliant and had a high probability of completing the study in the opinion of the investigator.
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- Women were either surgically sterile (had a documented bilateral oophorectomy and/or documented hysterectomy) or were postmenopausal (cessation of menses for more than 2 years).
- Informed consent was signed and dated by the subject and/or subject's legally acceptable representative, if applicable, in accordance with local regulations.
- The subject was 25 years or older at the time of obtaining informed consent.
- The subject had no evidence of cognitive impairment by medical history.
- The subject had a Mini-Mental State Examination (MMSE) score of =< 27.
- The subject had a Clinical Dementia Rating (CDR) of 0.
- The subject had an MRI image as part of the screening visit of sufficient diagnostic quality and consistent with normal brain function (details provided in the associated Imaging Manual) for volume of interest (VOI) definition and partial volume correction.
- The subject was 55 years or older at the time of obtaining informed consent.
- The subject met National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for clinical pAD and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV]), 4th Edition, criteria for AD (DSM-IV criteria, American Psychiatric Association 1994).
- The subject had an MMSE score of 15 to 26 (inclusive) and a CDR of 0.5, 1 or 2.
- The subject had a score of =< 4 on the Modified Hachinski Ischemic scale.
- The subject had an appropriate caregiver capable of accompanying the subject on all study visits.
- The subject had an MRI image as part of the screening visit consistent with the diagnosis of pAD and of sufficient diagnostic quality (details provided in the associated Imaging Manual) for VOI definition and partial volume correction.
- The subject was 55 years or older at the time of obtaining informed consent.
- The subject met Petersen criteria for aMCI.
- The subject had an MMSE score of 27 to 30 (inclusive) and a CDR of 0 to 0.5.
- The subject had a score of =< 4 on the Modified Hachinski Ischemic Scale.
- The subject had an appropriate caregiver/companion capable of accompanying the subject on all study visits if necessary and applicable according to local regulations.
- The subject had an MRI image as part of the screening visit consistent with the diagnosis of aMCI and of sufficient diagnostic quality (details provided in Imaging Manual) for VOI definition and partial volume correction.
Who cannot join
- The subject was not able to complete the study procedures as judged by the investigator.
- The subject had received ionizing radiation exposure of more than 1 mSv (except arising from head computed tomography [CT]) in the last 12 months or was determined unsuitable by the investigator as a result of radiation exposure in the past.
- The subject had a known or suspected hypersensitivity/allergy to [18F] flutemetamol or to any of its excipients.
- Female subjects who were of childbearing potential, pregnant, or nursing.
- The subject had a history of alcohol and/or drug abuse within the last 2 years based upon a review of medical records or reported medical history.
- The subject had a contraindication for MRI or PET (including, but not limited to, claustrophobia, pacemaker, the presence of metallic fragments, or cochlear implant).
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- The subject had participated in a clinical trial using an investigational medicinal product (IMP) within 30 days of dosing.
- The subject had positive serology for HBs antigen, HCV antibody, HIV antibody or serologic test for syphilis.
- The subject regularly took medication with a known anticholinergic effect (which could have impaired memory) within the prior 3 months.
- The subject had a history of head injury associated with significant loss of consciousness that, in the opinion of the investigator, would have interfered with the interpretation of PET images.
- The subject had any clinically significant medical or neurological condition or any clinically significant abnormality on physical, neurological or laboratory examination.
- The subject had a family history of pAD (more than 1 first degree relative with the diagnosis of pAD).
- The subject had a significant neurological or psychiatric disorder (including, but not limited to, major depression, schizophrenia, mania, etc.) other than pAD that may have affected cognition.
- The subject had a previous history of clinically evident stroke or significant cerebrovascular disease on brain imaging.
About this study
Official title: An Open-label Study to Assess Brain Uptake and Safety of Flutemetamol F 18 Injection in Japanese Subjects With Probable Alzheimer's Disease, Subjects With Amnestic Mild Cognitive Impairment and Healthy Volunteers
This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: healthy volunteers (HV), amnestic mild cognitive impairment (aMCI), and probable Alzheimer's disease (pAD), and to assess the reproducibility of brain uptake and of image interpretation. Subjects underwent open-label intravenous (i.v.) administration of Flutemetamol F 18 Injection and Positron emission tomography (PET) imaging of the brain. Blinded visual image reads were performed by 10 independent board-certified readers (5 Japanese and 5 non-Japanese) with nuclear medicine image interpretation experience. The blinded visual assessments were compared with the subject's clinical diagnoses, and the agreement between the image interpretations made by the 2 groups of readers (Japanese and non-Japanese) was determined.
Read the detailed description
This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: HV, aMCI, and pAD, and to assess the reproducibility of brain uptake and of image interpretation. The 3 comparison groups (HV, aMCI, and pAD) were defined by the subjects' main clinical diagnoses at study entry. Subjects underwent diagnostic quality anatomic brain magnetic resonance imaging (MRI), followed by open-label intravenous (i.v) administration of Flutemetamol F 18 Injection and PET imaging of the brain. Blinded visual image reads were performed by 10 independent board-certified readers (5 Japanese and 5 non-Japanese) with nuclear medicine image interpretation experience. The blinded visual assessments were compared with the subject's clinical diagnoses, and the agreement between the image interpretations made by the 2 groups of readers (Japanese and non-Japanese) was determined. Blinded visual assessments were also compared to quantitative image assessments (standardized uptake value ratio [SUVRs]). Inter-reader and intra-reader agreement was also assessed. Test-retest variability was evaluated following a second administration of Flutemetamol F 18 Injection given to a subset (N=5) of pAD subjects between 1 and 4 weeks after their first administration of Flutemetamol F 18 Injection.
- Conditions
- Mild Cognitive Impairment, Alzheimer's Disease, Healthy
- Being tested
- [18F] Flutemetamol
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F] FlutemetamolDrug
Also called GE067
PET brain imaging and Magnetic resonance brain imaging
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers | Experimental | 185 MBq [18F] Flutemetamol Receives: Drug: [18F] Flutemetamol |
| Mild cognitive impairment | Experimental | 185 MBq [18F] Flutemetamol Receives: Drug: [18F] Flutemetamol |
| Alzheimer's Disease | Experimental | 185 MBq [18F] Flutemetamol Receives: Drug: [18F] Flutemetamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Non-Japanese Readers
The performance of Flutemetanol F 18 injection in participants was determined by evaluation of the level of association between the blinded visual assessment of a participant's brain image and the participant's clinical diagnosis by 5 non-Japanese readers, who classified each participant's images as either normal or abnormal (raised) Flutemetanol F 18 uptake.
Measured: Up to 90 minutes after investigational medicinal product (IMP) administration
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Japanese Readers
The performance of Flutemetanol F 18 injection in participants was determined by evaluation of the level of association between the blinded visual assessment of a participant's brain image and the participant's clinical diagnosis by 5 Japanese readers, who classified each participant's images as either normal or abnormal (raised) Flutemetanol F 18 uptake.
Measured: Up to 90 minutes after IMP administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2016 (estimated)
- Study startOct 2012
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by GE HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- GE Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Levent Ture, Study director, GE Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02813070
- Sponsor's protocol ID
- GE067-017
- Status last verified
- May 2017
- First submitted
- 15 Jun 2016
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Miki T, Shimada H, Kim JS, Yamamoto Y, Sugino M, Kowa H, Heurling K, Zanette M, Sherwin PF, Senda M. Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer's disease, subjects with amnestic mild cognitive impairment and healthy volunteers. Ann Nucl Med. 2017 Apr;31(3):260-272. doi: 10.1007/s12149-017-1154-7. Epub 2017 Feb 8.
PubMed 28181118
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Assess Brain Uptake and Safety of Flutemetamol F 18 Injection in Japanese Subjects With Probable Alzheimer's Disease, Subjects With Amnestic Mild Cognitive Impairment and Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02813070
- Acronym / sponsor ID
- GE067-017
- Conditions
- Mild Cognitive Impairment, Alzheimer's Disease, Healthy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- GE HealthcareIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 24 Jun 2016 (estimated)
- Results
- Posted 5 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: healthy volunteers (HV), amnestic mild cognitive impairment (aMCI), and probable Alzheimer's disease (pAD), and to assess the reproducibility of brain uptake and of image interpretation. Subjects underwent open-label intravenous (i.v.) administration of Flutemetamol F 18 Injection and Positron emission tomography (PET) imaging of the brain. Blinded visual image reads were performed by 10 independent board-certified readers (5 Japanese and 5 non-Japanese) with nuclear medicine image interpretation experience. The blinded visual assessments were compared with the subject's clinical diagnoses, and the agreement between the image interpretations made by the 2 groups of readers (Japanese and non-Japanese) was determined.
Detailed description
This was a Phase 2, multicenter study to assess the extent and patterns of [18F] flutemetamol uptake in the brains of 3 groups of Japanese subjects: HV, aMCI, and pAD, and to assess the reproducibility of brain uptake and of image interpretation. The 3 comparison groups (HV, aMCI, and pAD) were defined by the subjects' main clinical diagnoses at study entry. Subjects underwent diagnostic quality anatomic brain magnetic resonance imaging (MRI), followed by open-label intravenous (i.v) administration of Flutemetamol F 18 Injection and PET imaging of the brain. Blinded visual image reads were performed by 10 independent board-certified readers (5 Japanese and 5 non-Japanese) with nuclear medicine image interpretation experience. The blinded visual assessments were compared with the subject's clinical diagnoses, and the agreement between the image interpretations made by the 2 groups of readers (Japanese and non-Japanese) was determined. Blinded visual assessments were also compared to quantitative image assessments (standardized uptake value ratio [SUVRs]). Inter-reader and intra-reader agreement was also assessed. Test-retest variability was evaluated following a second administration of Flutemetamol F 18 Injection given to a subset (N=5) of pAD subjects between 1 and 4 weeks after their first administration of Flutemetamol F 18 Injection.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | Experimental | Drug: [18F] Flutemetamol185 MBq [18F] Flutemetamol |
| Mild cognitive impairment | Experimental | Drug: [18F] Flutemetamol185 MBq [18F] Flutemetamol |
| Alzheimer's Disease | Experimental | Drug: [18F] Flutemetamol185 MBq [18F] Flutemetamol |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- The subject had at least 6 years of education.
- The subject was of first-order Japanese descent.
- The subject exhibited adequate visual, auditory and communication capabilities, and was willing and able to complete standard tests of cognitive function.
- The subject's general health was adequate to comply with all study procedures, as ascertained by review of their medical history, and laboratory and physical examinations, which was performed within 45 days before the first administration of Flutemetamol F 18 Injection.
- The subject (and the caregiver, if relevant) was/were compliant and had a high probability of completing the study in the opinion of the investigator.
Key exclusion criteria (14 listed)
- The subject was not able to complete the study procedures as judged by the investigator.
- The subject had received ionizing radiation exposure of more than 1 mSv (except arising from head computed tomography [CT]) in the last 12 months or was determined unsuitable by the investigator as a result of radiation exposure in the past.
- The subject had a known or suspected hypersensitivity/allergy to [18F] flutemetamol or to any of its excipients.
- Female subjects who were of childbearing potential, pregnant, or nursing.
- The subject had a history of alcohol and/or drug abuse within the last 2 years based upon a review of medical records or reported medical history.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F] FlutemetamolAlso: GE067PET brain imaging and Magnetic resonance brain imaging | Drug | Alzheimer's Disease, Healthy volunteers, Mild cognitive impairment |
Primary outcome
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Non-Japanese Readers
Time frame: Up to 90 minutes after investigational medicinal product (IMP) administration
The performance of Flutemetanol F 18 injection in participants was determined by evaluation of the level of association between the blinded visual assessment of a participant's brain image and the participant's clinical diagnosis by 5 non-Japanese readers, who classified each participant's images as either normal or abnormal (raised) Flutemetanol F 18 uptake.
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Japanese Readers
Time frame: Up to 90 minutes after IMP administration
The performance of Flutemetanol F 18 injection in participants was determined by evaluation of the level of association between the blinded visual assessment of a participant's brain image and the participant's clinical diagnosis by 5 Japanese readers, who classified each participant's images as either normal or abnormal (raised) Flutemetanol F 18 uptake.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28181118Miki T, Shimada H, Kim JS, Yamamoto Y, Sugino M, Kowa H, Heurling K, Zanette M, Sherwin PF, Senda M. Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer's disease, subjects with amnestic mild cognitive impairment and healthy volunteers. Ann Nucl Med. 2017 Apr;31(3):260-272. doi: 10.1007/s12149-017-1154-7. Epub 2017 Feb 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Levent Ture study director
GE Healthcare
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing [18F] Flutemetamol in people with Mild Cognitive Impairment and Alzheimer's Disease, run by GE Healthcare.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blinded Visual Assessment of Positron Emission Tomography (PET) Imaging and Clinical Diagnosis by Non-Japanese Readers (time frame: Up to 90 minutes after investigational medicinal product (IMP) administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02813070, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.